PT  - JOURNAL ARTICLE
AU  - Spielberg, S P
AU  - Gordon, G B
AU  - Blake, D A
AU  - Mellits, E D
AU  - Bross, D S
TI  - Anticonvulsant toxicity in vitro: possible role of arene oxides.
DP  - 1981 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 386--389
VI  - 217
IP  - 2
4099  - http://jpet.aspetjournals.org/content/217/2/386.short
4100  - http://jpet.aspetjournals.org/content/217/2/386.full
SO  - J Pharmacol Exp Ther1981 May 01; 217
AB  - Human lymphocytes incubated with a mouse hepatic microsomal drug metabolizing system were used to study the cytotoxicity of four anticonvulsants. In vitro toxicity assessed by trypan blue dye exclusion was significantly greater for compounds with relatively high clinical toxicity (mephenytoin and phenacemide) than those with only rare cytotoxic complications (phenytoin and phenobarbital). No toxicity occurred in the absence of microsomes and toxicity was enhanced by inhibitors of epoxide hydrolase suggesting that the cytotoxicity of the drugs may result from arene oxide metabolites. In vivo, the covalent binding of such metabolites to cell macromolecules could lead to cell death and, by acting as haptens, to secondary hypersensitivity reactions. The method may be useful in assessing the potential of a drug for toxicity, the mechanism of cell damage and individual differences in cell defenses within the human population.